Randomized trial of irinotecan drug combination versus standard therapy as first-line treatment in patients with locally advanced or metastatic small bowel adenocarcinoma

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What is this study about?

The trial focuses on adults with locally advanced or metastatic small bowel adenocarcinoma, a rare cancer that has spread beyond the small intestine. Two chemotherapy approaches are being compared: a three‑drug regimen known as mFOLFIRINOX, which contains irinotecan, oxaliplatin, and fluorouracil together with calcium folinate to protect normal cells, and a two‑drug regimen called FOLFOX, which includes oxaliplatin and fluorouracil with calcium folinate.

The purpose of the study is to determine which of the two regimens works better as the first treatment given for this cancer. Participants will be randomly assigned to receive either the three‑drug or the two‑drug combination, with treatment given through an IV infusion every two weeks for several cycles, followed by regular check‑ups.

During the study, imaging scans will be performed to see if the tumor grows or shrinks, allowing calculation of measures such as progression‑free survival (the time a patient lives without the disease getting worse) and overall survival (the time a patient lives after starting treatment). The rate of tumor shrinkage, called objective response rate, and the depth of response will also be recorded. Patients will complete a short questionnaire about quality of life, and any side effects will be closely monitored and graded for seriousness.

1 randomization and treatment assignment

after enrollment you are randomly assigned to receive either the modified folfirinox regimen or the folfox regimen. this assignment determines which combination of medicines you will receive during the trial.

2 baseline assessments

before the first dose, imaging studies (such as CT scans) are performed to document the current size and location of the cancer.

blood samples are taken to evaluate organ function and to calculate the correct dosage of each medication based on your body surface area.

3 first treatment cycle – medication administration

on the first day of the cycle you receive a series of infusions and an injection according to the study protocol.

the infusion includes oxaliplatin at a dose of 85 mg per square meter of body surface area, irinotecan at a dose of 150 mg per square meter, and calcium folinate at a dose of 400 mg per square meter.

following the infusions, an injection of fluorouracil is given at a dose of 2400 mg per square meter.

4 subsequent treatment cycles

the same set of medicines (oxaliplatin, irinotecan, calcium folinate, and fluorouracil) is given in each additional cycle, using the same dosages based on your body surface area.

each cycle follows the same administration pattern as the first cycle, as defined by the trial schedule.

5 regular monitoring

periodic blood tests are performed to monitor organ function and detect any side effects.

imaging studies are repeated at scheduled intervals to assess whether the cancer is responding to treatment.

any side effects are evaluated and may lead to dose adjustments or temporary interruptions, according to the study guidelines.

6 treatment discontinuation and follow‑up

treatment is stopped if the disease progresses, if unacceptable side effects occur, or after the predetermined number of cycles is completed.

after stopping the study medication, you continue with regular follow‑up visits to monitor overall survival and quality of life.

Who Can Join the Study?

Give a signed informed consent indicating you agree to join the study.
If you are not taking blood‑thinning medication, your blood clotting tests (INR and PTT) must be less than 1.5 times the normal upper limit; people who are on approved blood thinners are also allowed.
You must be able to process the chemotherapy drug fluorouracil normally. This means you have either taken similar drugs before without serious side effects, or you have had a normal test for the enzyme DPD that breaks down the drug. If a DPD test shows a mild deficiency, the dose will be reduced by half.
Women who could become pregnant must have a negative pregnancy test within 14 days before starting the study and must agree to avoid pregnancy by either staying abstinent or using highly effective birth control (failure rate less than 1 % per year) during treatment and for six months after the last dose. Men with partners who could become pregnant must also use condoms plus another highly effective method, stay abstinent, or both, and must not donate sperm during this time.
You must be at least 18 years old when you sign the consent form.
Your diagnosis must be confirmed by a tissue test showing small bowel adenocarcinoma.
Your tumor must be microsatellite stable or have normal mismatch repair function, as shown by standard lab tests.
Your cancer must be judged by the study doctors as either locally advanced and not removable by surgery, or it must have spread (metastasized) to other parts of the body.
You must not have received any cancer‑directed treatment for this advanced or metastatic disease before joining the trial.
You need to have at least one tumor measurement that can be evaluated using the standard criteria called RECIST 1.1.
Your overall health level, measured by the ECOG performance status, must be 0‑2 (able to care for yourself). If you are older than 70, the status must be 0 or 1.
Your blood, liver and kidney function must be adequate, shown by lab results that meet the following limits: absolute neutrophil count ≥ 1.5 × 10⁹/L (1500/µL), hemoglobin ≥ 80 g/L (8 g/dL) with or without transfusion, platelet count ≥ 100 × 10⁹/L (100,000/µL) without transfusion, total bilirubin ≤ 1.5 × upper limit of normal, AST and ALT ≤ 2.5 × upper limit of normal (or ≤ 5 × if due to liver metastasis), and estimated kidney filtration rate ≥ 50 mL/min or serum creatinine ≤ 1.5 × upper limit of normal.

Who Cannot Join the Study?

Having cancer of the ampulla of Vater (the small opening where bile and pancreatic fluids enter the intestine).
Having severe long‑lasting wounds that do not heal, open sores (ulcerous lesions), or a broken bone that has not been treated.
Being known to be allergic (hypersensitive) to any of the chemotherapy medicines 5‑FU, leucovorin, capecitabine, irinotecan, oxaliplatin, or to any of the other ingredients in the drug.
Having taken or currently taking the antiviral drug brivudine.
Having nerve damage in the hands or feet (peripheral neuropathy) that causes functional problems worse than a mild level (greater than grade 1 on the CTCAE grading system).
Using Johannis herbs (herbal preparations) at the same time as the study drugs.
Having pernicious anemia or another type of large‑cell anemia caused by a lack of vitamin B12.
Having had major surgery, an open tissue biopsy, or a serious injury within the past 21 days that could interfere with the study treatment.
Having any other disease, metabolic problem, physical‑exam finding, or lab result that makes the study drug unsafe, could affect the study results, or puts the patient at high risk of complications.
Having a history of another cancer, unless the other cancer: (a) has been absent for at least three years, (b) was a basal cell or squamous cell skin cancer, in‑situ cervical, breast, prostate, or stage I uterine cancer that was completely removed, or (c) is a cancer with a very good (≥ 80 %) five‑year survival chance and does not need active treatment now.
Having alcohol abuse, drug dependence, or substance abuse that could prevent following the study rules.
Having a current or imminent intestinal blockage (ileus). Patients whose ileus was treated and resolved are allowed.
Being pregnant or breastfeeding.
Having taken part in another clinical trial or experimental drug treatment within the last 28 days (or within five drug half‑lives, whichever is longer) or being enrolled in another trial at the same time.
Being financially or otherwise dependent on the study sponsor, investigator, or study site.
Being confined to a facility by a court or administrative order.
Being unable to give informed consent because you cannot understand the nature and importance of the trial.
Being unable to attend the required medical follow‑up visits because of geographic, social, or psychological reasons.
Having received chemotherapy before for metastatic or unresectable disease.
Having moderate to severe heart failure (New York Heart Association class III or higher).
Having had a heart attack (myocardial infarction) or a heart‑opening procedure called percutaneous transluminal coronary angioplasty (PTCA), with or without a stent, within the past 6 months.
Having unstable chest pain from heart disease (unstable angina).
Having a dangerous irregular heartbeat (arrhythmia) that is worse than grade 2 on the CTCAE scale despite medication.
Having ongoing side effects that are moderate or worse (grade > 2 on the CTCAE), especially nerve damage.
Having an active infection that is not under control.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Rostock University Medical Center	Rostock	Germany

Other Sites

Site Name	City	Country
ELBLANDKLINIKEN Stiftung & Co. KG	Riesa	Germany
Kdfpthsf Srzbcqcsw Riavevr	Rostock	Germany
Keqzfkbo Cmxtnqli gpksa	Chemnitz	Germany
Dji Vfaxigesqsfwgu Mlp Gako	Landshut	Germany
Rfjzaljmk Kpiozoqr Nufwx Gssf	Neuss	Germany
Hcabve Ktbwyzsr Bot Sttdnb Gaeb	Bad Saarow	Germany
Kcnwccuxmhl Nmtbdbbc Gnpi	Frankfurt	Germany
Utozxjnkxpficksgwvcot Asggrjku	Augsburg	Germany
Shc Jstnivhjhnwicur Wakwjnjww Ghgi	Wiesbaden	Germany
Pdzoafmhdyatthperv	Wuppertal	Germany
Mthbyi Hhkeefjh Hdeqt Ulxpsjplklxqdruaohex ddl Rbdacxlhjwaqphfr Btqlrk	Herne	Germany
Hwkhge Khierlqq Evmy vnw Bdacaco Gyny	Berlin	Germany
Kkadpyxv Opkuoxaik Akp	Oldenburg In Holstein	Germany
Kxelqzqn ddo Ukfniwzpkzah Mzbxqewm Anp	Munich	Germany
Cxgdovi Uoywgijncvksumopkltc Bqddkc Ksu	Berlin	Germany
Mwv as Kmouzmpm Afvserzhzzthxt Zmcletkqnph Hrnbveufase &pirfhr Osyvuenat	Aschaffenburg	Germany

Trial status

Country	Status	Recruitment Start
Germany	Not yet recruiting	03.08.2026

Trial locations

Investigated Drugs:

Irinotecan is a chemotherapy medicine that stops cancer cells from copying their DNA, which prevents them from growing and spreading. In this study it is given through an IV infusion as one of the three drugs that make up the modified FOLFIRINOX treatment plan.

Oxaliplatin is a chemotherapy drug that damages the DNA inside cancer cells, making it harder for them to survive. It is used in both the FOLFOX and the modified FOLFIRINOX treatment groups and is also given by IV infusion.

5‑Fluorouracil (5‑FU) is a chemotherapy agent that blocks the building blocks needed for DNA and RNA, which stops cancer cells from multiplying. In the trial it is administered by injection and is a key part of both treatment regimens.

Calcium Folinate (often called leucovorin) is not a chemotherapy drug itself, but it helps the body make 5‑FU work better against cancer cells. It is given by injection together with 5‑FU in the study.

Investigated Diseases:

Small intestine adenocarcinoma

Locally advanced or metastatic small bowel adenocarcinoma – This disease is a cancer that begins in the glandular cells lining the small intestine. It can grow outward from the inner surface to involve deeper layers of the bowel wall. The tumor may spread to nearby lymph nodes and surrounding tissues, which is described as locally advanced. Cancer cells can also travel through the bloodstream or lymphatic system to distant organs, leading to metastatic disease. As the tumor expands, it can cause narrowing of the intestinal lumen, leading to blockage or changes in bowel habits.

Trial ID:

2025-524131-39-00

Protocol code:

FIRE-12

Trial Phase:

Therapeutic use (Phase IV)

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Randomized trial of irinotecan drug combination versus standard therapy as first-line treatment in patients with locally advanced or metastatic small bowel adenocarcinoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?